Abstract
The recent definition of the pathways of generation and structures of diverse products of the lipoxygenation of arachidonic acid has established the identity of a new family of mediators of hypersensitivity and inflammation. Studies of the effects of these mediators have shown that leukotrienes C, D, and E, the constituents of the slow-reacting substance of anaphylaxis (SRS-A), are extremely potent smooth muscle contractile and vasoactive factors. Leukotriene B is a highly active stimulus of neutrophil and eosinophil functions and suppresses the immunological capabilities of T lymphocytes. The development of specific and sensitive radioimmunoassays has permitted the detection of elevated concentrations of leukotrienes in tissues or exudates in several diseases, including asthma, diverse allergic states, adult respiratory distress syndrome, psoriasis, spondyloarthritis, and gout. The application of selective inhibitors and antagonists of leukotrienes will clarify their pathogenetic contributions in human diseases and may yield new therapeutic approaches.
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Borgeat P, Samuelsson B: Metabolism of arachidonic acid in polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem 254-7865–7869, 1979
Murphy RC, Hammarstrom S, Samuelsson B: Leukotriene C: A slow reacting substance from murine mastocytoma cells. Proc Natl Acad Sci USA 76:4275–4279, 1979
Borgeat P, Samuelsson B: Arachidonic acid metabolism in polymorphonuclear leukocytes: Unstable intermediate in formation of dihydroxy acids. Proc Natl Acad Sci USA 76:3213–3217, 1979
Samuelsson B: Leukotrienes: A new class of mediators of immediate hypersensitivity reactions and inflammation.In Advances in Prostaglandin, Thromboxane, and Leukotriene Research, B. Samuelsson, R Paoletti, P Ramwell (eds). New York, Raven Press, 1983, Vol 11, pp 1–13
Goetzl EJ, Scott WA III: Regulation of cellular activities by leukotrienes and other lipoxygenase products of arachidonic acid. J Allergy Clin Immunol (Suppl) (in press), 1984
Marcus AJ, Broekman MJ, Safier LB, Ullman HL, Islam N, Serhan CN, Rutherford LE, Korchak HM, Weissmann G: Formation of leukotrienes and other hydroxy acids during platelet-neutrophil interactions in vitro. Biochem Biophys Res Commun 109:130–137, 1982
Pawlowski NA, Kaplan G, Hamill AL, Cohn ZA, Scott WA: Arachidonic acid metabolism by human monocytes: Studies with platelet-depleted cultures. J Exp Med 158:393–412, 1983
Jubiz W, Radmark O, Lindgren JA, Malmsten C, Samuelsson B: Novel leukotrienes: products formed by initial oxygenation of arachidonic acid at C-15. Biochem Biophys Res Commun 99:976–986, 1981
Holtzman MJ, Finkbeiner WE, Goetzl EJ, Nadel JA: Selective generation of leukotriene B4 and 15-hydroxy-eicosatetraenoic acid by human tracheal epithelial cells. Fed Proc (in press), 1984
Goetzl EJ: The conversion of leukotriene C4 to isomers of leukotriene B4 by human eosinophil peroxidase. Biochem Biophys Res Commun 106:270–275, 1982
Lee CW, Lewis RA, Corey EJ, Barton A, Oh H, Tauber AI, Austen KF: Oxidative inactivation of leukotriene C4 by stimulated human polymorphonuclear leukocytes. Proc Natl Acad Sci USA 79:4166–4170, 1982
Goetzl EJ, Pickett WC: Novel structural determinants of the human neutrophil chemotactic activity of leukotriene B4. J Exp Med 153:482–487, 1981
Goetzl EJ, Brindley LL, Goldman DW: Enhancement of human neutrophil adherence by synthetic leukotriene constituents of the slow-reacting substance of anaphylaxis. Immunology 50:35–41, 1983
O'Flaherty JT, Hammett MJ, Shewmake TB, Wykl RL, Love SH, McCall CE, Thomas MJ: Evidence for 5,12-dihydroxy-6,8,10,14-eicosatetraenoate as a mediator of human neutrophil aggregation. Biochem Biophys Res Commun 103:552–558, 1981
Nagy L, Lee TH, Goetzl EJ, Pickett WC, Kay AB: Complement receptor enhancement and chemotaxis of human neutrophils and eosinophils by leukotrienes and other lipoxygenase products. Clin Exp Immunol 47:541–547, 1982
Payan DG, Brewster DR, Goetzl EJ: Binding properties of the substance P (SP) neuropeptide receptors on IM-9 human lymphoblastoid cells. Fed Proc (in press), 1984
Payan DG, Goetzl EJ: Specific suppression of human T-lymphocyte function by leukotriene B4. J Immunol 131:551–553, 1983
Goodman MG, Weigle WO: Regulation of B-lymphocyte proliferative responses by arachidonate metabolites: Effects on membrane-directed versus intracellular activators. J Allergy Clin Immunol (Suppl) (in press), 1984
Voorhees JJ: Modulation of epidermal cell division and growth by oxygenation products of arachidonic acid. J Allergy Clin Immunol (Suppl) (in press), 1984
Omini C, Folco GC, Vigano T, Rossoni G, Brunelli G, Berti F: Leukotriene C4 induces generation of PGI2 and TxA2 in guinea pigsin vivo. Pharmacol Res Commun 13:633–640, 1981
Goldman DW, Goetzl EJ: Specific binding of leukotriene B4 to receptors on human polymorphonuclear leukocytes. J Immunol 129:1600–1604, 1982
Krilis S, Lewis RA, Corey EJ, Austen KF: Specific receptors for leukotriene C4 on a smooth muscle cell line. J Clin Invest 72:1516–1519, 1983
Kuehl FA: Lung tissue receptors for leukotrienes. J Allergy Clin Immunol (Suppl) (in press), 1984
Ford-Hutchinson AW: Leukotriene involvement in pathological processes. J Allergy Clin Immunol (Suppl) (in press), 1984
Dáhlen S, Hansson G, Hedqvist P, Björk T, Granström E, Dáhlen B: Allergen challenge of lung tissues from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4. Proc Natl Acad Sci USA 80:1712–1716, 1983
Cromwell O, Walport MJ, Morris H, Taylor GW, Hodson ME, Batten J, Kay AB: Identification of leukotrienes D and B in sputum from cystic fibrosis patients. Lancet 8239:164–165, 1981
Stenmark KR, James SL, Voelkel NF, Toews WH, Reeves JT, Murphy RC: Leukotrienes C4 and D4 in neonates with hypoxemia and pulmonary hypertension. N Engl J Med 309:77–80, 1983
Matthay MA, Eschenbacher WC, Goetzl EJ: Leukotrienes in the airway edema fluid of patients with the adult respiratory distress syndrome. Clin Res (in press), 1984
Brain SD, Camp RDR, Dowd RM, Kobza-Black A, Wollard PMN, Mallet AI, Greaves MW: Psoriasis and leukotriene B4. Lancet 8301:762–763, 1982
Talbot SF, Atkins P, Zweiman B, Goetzl E: In vivo antigen-induced release of leukotrienes in human skin. Clin Res (in press), 1984
Rae SA, Davidson EM, Smith MJH: Leukotriene B4: An inflammatory mediator in gout. Lancet 8308:1122–1123, 1982
Klickstein LB, Shapleigh C, Goetzl EJ: Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis. J Clin Invest 66:1166–1170, 1980
Sharon P, Stenson WF: Production of leukotrienes by colonic mucosa from patients with inflammatory bowel disease. Gastroenterology 84:1306(A), 1983
Hammarstrom S: Leukotriene C5: A slow-reacting substance derived from eicosapentaenoic acid. J Biol Chem 255:7093–7094, 1980
Goldman DW, Pickett WC, Goetzl EJ: Human neutrophil chemotactic and degranulating activities of leukotriene B5 (LTB5) derived from eicosapentaenoic acid. Biochem Biophys Res Commun (in press), 1984
Sanders TAB, Vickers M, Haines AP: Effect on blood lipids and haemostasis of cod-liver oil, rich in eicosapentaenoic acid and docosahexanoic acids, in healthy young men. Clin Sci 61:317–324, 1981
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Goetzl, E.J., Payan, D.G. & Goldman, D.W. Immunopathogenetic roles of leukotrienes in human diseases. J Clin Immunol 4, 79–84 (1984). https://doi.org/10.1007/BF00915039
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DOI: https://doi.org/10.1007/BF00915039